"Don't Work on Things That Don't Work"

Peptidic GLP-1R agonists have received significant media coverage over the past year for their astounding efficacy in several indications. While most of the recent fanfare has been related to their role in weight loss, GLP-1R agonists have been a mainstay of the type 2 diabetes treatment landscape for the past 2 decades. GLP-1R agonists have also recently shown efficacy in reducing heart disease risk and treating certain chronic kidney diseases. Here’s a recap of the March 14th, 2024, Flash Talk, from Oliver Philps.

The highly anticipated First Time Disclosures session at the ACS Spring 2024 Meeting in New Orleans, organized by Nicole Goodwin and H. Rachel Lagiakos, presented a variety of new orally available small molecules. In case you missed any of these exciting molecules, from Oric’s CD73 inhibitor to Deciphera’s first-in-class ULK1/2 inhibitor, this article provides the structures and targets for the novel molecules disclosed at the session.

Momelotinib is a JAK inhibitor approved by the FDA in September 2023 for treating myelofibrosis. Last year, the molecule’s co-inventors, Andrew Wilks and Christopher Burns, gave a Drug Hunter Flash talk about the development of this drug with a fascinating mechanism of action.

In celebration of the molecule’s advancement, here we recap their brilliant story, including Wilks’ discovery of the JAK kinases and how he gave them their name, and the long, sometimes fraught journey of momelotinib through several companies before its acquisition and commercialization by GSK.

Imagine having access to an almost infinite amount of chemical space that could include the next blockbuster medicine waiting to be discovered. The challenge for medicinal chemists is balancing the exploration of this vast space in early drug discovery with the need for focused exploration in later stages. This article explores the genesis of a new AI-powered drug design tool, AIDDISON™ from MilliporeSigma, and how this platform can benefit discovery teams around the world.

Among the small molecule highlights in January’s news were a $100M+ Series A for a PARP1 + PI3Kα-focused company, clinical data with an SLC inhibitor for PKU, a 5-HT2C superagonist for seizures, and a NK1,3 dual antagonist for women’s health. A novel anti-obesity agent from phenotypic screening also made headlines, and the close of a major acquisition may bring relief to the industry. You can read about these notable scientific highlights and more below.